Effects of phosphodiesterase-4 inhibitor Ro 20-1724 on learning and memory function after ketamine anesthesia and cAMP/PKA-CREB-BDNF signal pathway in immature rats / 中华行为医学与脑科学杂志

ABSTRACT

Objective To observe a new phosphodiesterase-4 inhibitor Ro 20-1724 on ketamine anesthesia-induced learning and memory impairment and cAMP/PKA-CREB-BDNF signal pathway in immature rats.Methods Twenty-four 21 day-old SD rats were randomly divided into 4 groups (n=6 each)control group (group C) ;ketamine group (group K) ;ketamine+Ro 20-1724 group(group K+Ro) and ketamine+vehicle (0.1％ ethanol) group (group K+E).Ketamine 70 mg/kg was injected intraperitoneally(IP) once a day for 7 consecutive days in groups K,K+Ro,and K+E.Ro 20-1724 0.5 mg/kg and equal volume of vehicle were injected IP at 30 min after IP ketamine each time respectively.Morris water maze was used to assess learning and memory ability after 2 days normal feeding,the escape latency and frequency of passing the platform were recorded.The animals were killed after water maze test and the cAMP,PKA,p-CREB,and BDNF protein expression in hippocampus were detected.Results Repetitive ketamine anesthesia significantly prolonged the escape latency (P＜0.01),decreased the frequency of passing the platform(P＜0.01),and down-regulated the expression of cAMP,PKA,p-CREB,and BDNF protein ((280±31) pmol/mg vs (210± 19) mol/mg,P＜0.01 ; 1.32±0.11 vs 1.13±0.12,P＜0.01 ; 2.61 ±0.22 vs 2.03 ± ±0.19,P＜0.01 ; 1.51 ±0.14 vs 1.16±0.10,P＜0.05) ; Compared with group K,Ro 20-172,significantly attenuated the escape latency time(P＜0.05,P＜0.01)and increased the frequency of passing the platform(P＜0.01),and ameliorated the expression of cAMP,PKA,p-CREB,and BDNF protein ((210± 19) pmoL/mg vs (240± 27) pmol/mg,P ＜0.05;1.13±0.12 vs 1.28±0.12,P＜0.05;2.03±0.19 vs 2.32±0.21,2.32±0.21;1.16±0.10 vs 1.37±0.11,P＜0.01).There was no difference between group K+Ro and group C,and between group K+E and group K(P＞0.05).Conclusion ketamine anesthesia-induced learning and memory impairment can be improved by Ro 20-1724,and cAMP/PKA-CREB-BDNF signal pathway in hippocampus participated in the changes.